Casting gelatin tablets



y 8, 1951 J. c. BIRD ETAL 2,552,027

CAST ING GELATIN TABLETS Filed Jan. 1'7, 1948 INVENTORS Jfi/WY 6.5m:zwzopa/Pz a. POCHOW,

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ATTORNEY Patented May 8, 1951 CASTING GELATIN TABLETS John 0. Bird,Pleasantville, N. Y., and Theodore G. Rochow, Darien, 'C0nn., assignorsto American Cyanamid Company, New York, N. Y., a corporation of MaineApplication January 17, 1948, Serial No. 2,938

1 Claim. 1

With the advance in the progress of science it has become desirable toadminister various therapeutic agents to both man and animals. Variousmethods of administration are used among the most eflicient of which isto incorporate the various agents in a matrix and administer separateportions orally, as desired.

In the past gelatin has been used as such a matrix and in the gelatinhas been dispersed various therapeutic agents particularly vitamins.I-Ieretofore, considerable difficulty has been encountered becausegelatin in its plastic state is so sticky that it is extremely diflicultto handle and a large number of various forms of molds have been used.In the past a standard method was to form temporary cavities in powderedstarch, cast the gelatin tablets in the starch and then coat the tabletswith clear gelatin by dipping in such fashion that the liquid gelatin inthe dipping process did not come in contact with the supporting members.

The starch molds could be used for only one molding cycle and thuscostly and time-consuming, mold-making facilities were required as partof the gelatin-forming process. Moreover, the gelatin tablets were leftwith a coating of starch particles, requiring the extra step of dippinginto liquid gelatin.

It is an object of the present invention to provide a method wherebyvarious matrices particularly those containing gelatin may be cast inmolds made of Teflon.

It is an object of this invention to provide a method wherebypharmaceutical substances may be incorporated into a matrix which iscast into an individual dose tablet in such quantities as .may bedesired.

It is a further object to provide a method whereby gelatin tablets maybe rapidly and readily cast in final form without additional treatment.To more particularly illustrate and describe the invention theaccompanying drawings and specification show certain embodimentsthereof; additional objects and advantages will become apparent inconnection therewith.

In the accompanying drawings:

Figure 1 shows a front elevation of a castin machine. I

Figure 2 shows a top view of a single mold cavity.

Figure 3 shows a sectional view of such a mold cavity containing a casttablet.

Figure 4 shows a series of such molds arranged in a continuous strip.

of polytetrafluoroethylene.

in the literature and in the patents of others, as set forth forexample, in Patent No. 2,230,654,

to Roy J. Plunkett, February 4, 1941. The material has a waxy appearanceand is comparatively hard, usually of a light grayish color, may be cut,turned and worked more readily than brass and may be cut and worked oneither metal or woodworking machinery. The material may be burnished andpolished until highly reflective, until almost a specular finish isobtained. The mold, itself, may be molded from Teflon by the methods ofPatent 2,400,091 to Alfthan, or otherwise constructed. This mold is moreparticularly shown in Figures 2 and 3 and may consist of a round memberand may be turned from bar stock. It contains a cavity 2 which may beformed by an appropriately shaped drill and polished and burnished bymeans of successively .finer emery cloths or burnishing dust.

It is considered desirable that the bottom portion of this mold cavity 2be formed so as to match in curvature thatform produced on the upperface by the surface tension of the material to be cast, so that thefinal tablet is symmetrical. Whereas various or any desired form ofcavity may be used, for pharmaceutical purposes a symmetrical tablet ismore acceptable to the trade and accordingly, if the mold cavity 2 isshaped appropriately as shown in Figure 3, the tablet will possess thesame curvature on each side, being symmetrical and with a high finishgloss or sheen without further treatment or effort. If desired, forspecial purposes, a totally enclosed mold may be used, and any desiredshape tablet molded.

Figure 1 shows a device which is suitable for casting these individualtablets. The gelatin mixture prepared as described below, is shown at 4.This mix is placed in a vessel 5 which is surrounded by a jacket 6 orother heating means whereby hot water or other heat transfer medium maybe used to maintain the desired tern perature control. The cover l2 maybe provided with a filler tube 20, or other suitable filling means.Electrical elements and electric control are very satisfactory in aproperly insulated kettle.

In Figure 1 are shown entrance 1 and exit 8 pipes for the thermallyconditioning fluid. The interior of the kettle is shown with a stirrer 9to insure the homogeneity of the mix. This stirrer may be driven forexample by a gear wheel i and worm l l or by other suitable means whichmay be in turn supported by the cover l2 for the kettle. The cover isheld in position by any suitable means. Through the axis of this wheeland kettle is shown a plunger I3 which is reciprocable by means of anadjustable eccentric l4 so that this plunger is adjustably raised andlowered in a time adjustable fashion. If the temperature is keptconstant as the plunger raises and lowers, a uniform portion of the mixis trapped in the plunger cylinder i 5 which in turn acts as a pumpcasing thereby ejecting a uniform portion of the mix from the kettlethrough the orifice 16 with each functioning stroke of the plunger. Theexit orifice l6 and the plunger itself may be made from Teflon to insurethat the gelatin mix will not stick to and jam the measuring mechanism.The individual mold is supported by a carrier 11, the design of whichdepends upon the number, size and other conditions of the tablets to becast. The adjustable eccentric may be either manually or mechani- 'callyoperated and the molds on their support carrier I! either manually ormechanically operated and indexed so that a separate mold is positionedunder the orifice with each stroke of the plunger, thereby providing aseparate mold for each tablet. For large scale production a continuousstrip, as shown at l8, may be used containing any desired number of moldcavities l9 K which may be filled by an individual plunger or by a gangof plungers arranged to operate in suitably timed relationship.

In one particular modification individual Teflon molds were preparedfrom a rod of Teflon 1.9 cm. in diameter by cutting into discs .9 cm.high. Cavities were bored out by means of a specialboring tool, givingthe cavity a depth of 3 mm, with an elliptical bottom. The boredcavity'was polished using a mandrel with a corresponding shape,finishing it with a cloth charged with an aqueous suspension of powderedemery; progressively finer emery being used until a specularly smoothsurface was obtained. Such a polished cavity lasts indefinitely as thegelatin will not stick to it, and it remains clean and untarnished.

Other measuring mechanisms maybe used and other devices or arrangementsconstructed whereby uniform individual portions of gelatin are ejectedinto individual mold carriers. Various mechanical means will suggestthemselves whereby the manual or mechanical operations may be eased forthe operator provided that a sufflciently'largenumber of tablets is tobe cast to justify the more complex mechanism. As designed and shown themechanism is particularly suitable for use in an individual drug storein which tablets are to be made up by prescription for the specific useof an individual patient and "are to be cast only in such quantities asmay be desired for such purposes. Where large scale use is to be made ofthe tablets, as for example, in the'mass distribution of vitamin pills,a continuous strip and a mechanical feed mechanism U and in arefrigerator at 4 C. for four hours.

is more desirable. Such machines are well known in the pharmaceuticaland candy making fields.

Ecmmple 1 A base was made for a hard gelatin tablet by preparing acarrier mixture consisting of:

Parts Gelatin 50.4

Glycerine 2.8 Pharmaceutical mineral oil (medium grade) 2.8

Water 44.0

The gelatin,- glycerine, mineral oil and water were stirred thoroughlyat a temperature of approximately 65 C. until a uniform, homogeneousmixture was obtained. To this mixture was added 5 parts of apharmaceutical preparation consisting of vitamins A and D as oils andvitamins from the B group as powders. This material was stirred untilthoroughly incorporated into the gelatin matrix, and the homogeneousmixture dropped into the mold cavities. The material at this temperaturewas dropped in such portions that the mold cavity was slightly overfilled as shown in Figure 3, whereby the surface tension of the gelatincaused the tablets to assume the symmetrical shape as shown. Thematerial was allowed to dry at room temperature for two hours Soproduced, the material shrunk slightly and was easily removed from themold by means of a suction lifting-finger, or other means. The tabletsmay be additionally conditioned by drying as may be deemed advisable. Ifdesired more water may be added, thus requiring lower temperatures fordropping but longer periods for drying.

Example 2 A tablet was prepared by stirring together:

Parts Gelatin 14.8 Corn 'syr'u'p a 26.6 Medicated oil 26.6 Water 32.0

The water was warmed to 0., the gelatin added, corn syrup added and thenthe medicated oil. The medicated oil contained such a selection ofvitamins, cough inhibitors and other therapeutic agents as was deemeddesirable. The material was warmed at 75 to 80 C. and stirred untilsmooth, then dropped from an ordinary pipette into Teflon molds. Thematerial was allowed to dry at room temperature for several "days untilnon-sticky to touch and sufficiently rigid to maintain its shape. Theexact time depends upon room conditions.

Example 3 A vitamin-containing tablet was prepared containing on an ascast basis:

Parts Vitamin'A 'o'il (55,000 units per gram) 28.9 Vitamin 1) oil"(10,000 units per gram) 0.3 'Corn syrup a 25.0 Gelatin 13.9 Water 31.9

The gelatin was added to water, corn syrup added to the mixture andstirred until smooth at approximately 70 C. The vitamin oils added,mixed, and cast at a controlled temperature of 70 C. into Teflon molds.Ihe material was dried at room temperature until non-sticky.

After approximately 12 hours the material was sufiiciently non-sticky tomaintain its shape while being removed from the molds either by hand orby a suction lifter. The tablets maintained their shape afterapproximately 36 hours drying.

Example 4 A mixture was prepared as above containing:

Parts Vitamin A oil (15,755 units per gram) 20.8 Vitamin D oil (2466.units per gram) 0.7 Tocopherols, 30% 2.0 Vitamin B-1 0.6 Vitamin B-2 0.6Vitamin C 9.9 Niacinamide 1.5 Calcium pantothenatefl s 3.6 Gelatin 19.?Water 40.6

may be used as solids or dissolved in a mineral oil. Colored tables werecast from the following formulation:

Parts Water (containing certified food coloring) 20.0 Gelatin (acidtype) 26.8 Corn syrup 47.9 Glycerine 2.1 Mineral oil (containingvitamins) 3.2

The ingredients, in the order given, were mixed at room temperature,slowly to avoid entrapment of air, then slowly heated to a temperatureof 75 C., stirred until homogeneous and clear (about 2 hours) anddropped at a controlled temperature at 55 plus or minus 2 C. At a roomtemperature of C. the drops of gelatin mixture jelled in about minutesto the point where they Icould be rolled out of the Teflon mold.However, it is considered more desirable to allow them to dry for alonger period so that the material would be shape-stable and not deformwhen allowed to stand.

Other molded shapes as may be desired may be produced.

Food colors may be introduced into either the oil or water (gelatin)phase of the mix. Similarly water soluble materials may be introducedinto the water (glycerine) phase. Perfume or a flavor may be introducedinto the aqueous phase if desired.

The tablets cast from harder gelatin base that is, gelatin containing alower percentage of glycerine and mineral oil as set forth in Example 1are particularly useful for the administration of vitamins or otherpharmaceutical materials which should be released in the stomach ordigestive tract at comparatively slow rates. Gelatin tablets prepared inaccordance with Example 1 above when tested in synthetic gastric juiceat a temperature of 37 0., completely dissolved in an average time ofone and one half hours. This slow dissolution and release is frequentlybeneficial. In the past considerable diiiiculty has been experienced bythe sudden release to the stomach of fish oil or other odoriferousmaterials contained in soft gelatin capsules. This sudden releaseresults in objectionable regurgitation and the Vitamins are released sofast that they may not be properly assimilated. Further, the use ofTeflon appears to prevent oil droplets from coming to the interfacewhere they are easily broken. Even when fish liver oils are used, thefinished tablets do not possess a fish odor.

By the use of our molds, tablets are produced in the instant machinewhich permit the slow and uniform release of the desired materials overa prolonged period so that the concentration is low at all times andadequate for :a prolonged period. Such a method of production and such atablet has never been previously available on a small scale by theindividual druggist nor under reasonable economic conditions on a largescale by the pharmaceutical manufacturer because of the difficulty ofobtaining a mold material which could be used for a single casting andfinishing operation combined.

Whereas a preferred form of the invention has been shown herein it isunderstood that certain modifications and change in the constructiondetails in the several parts may be made without departing from thespirit of the invention.

We claim:

The method of preparing symmetrical gelatin vitamin tablets whichcomprises preparing a mixture consisting essentially of gelatin,glycerin, water and vitamins, mixing until homogeneous, droppin aportion of the homogeneous mixture into a polytetrafluoroethylene moldcavity, said cavity having a shape such that, (1) one surface of saidportion of the mixture is entirely free from contact with the walls ofthe cavity, permitting said surface to be shaped by surface tension,said free surface comprising the entire upper portion of said tablet,and (2) that portion of the mixture in contact with the walls of thecavity will have substantially the same configuration as the surfacetension gives to the free surface, permitting the mixture to harden, andremoving the thus formed symmetrical tablet from the mold.

JOHN C. BIRD. THEODORE G. ROCI-IOW.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 2,218,591 Taylor Oct. 22, 19402,403,476 Berry et a1 July 9, 1946 FOREIGN PATENTS Number Country Date2,488,446 Switzerland Nov. 15, 949

